ALK重排肾细胞癌(ALK-RCC)非常罕见,最近出版的第5版世界卫生组织肿瘤分类中分子定义的RCC亚型。在这项研究中,我们描述了9种来自临床病理的ALK-RCC,免疫组织化学,和分子遗传方面,支持和扩展先前研究对这种罕见的RCC亚组的观察结果。有6名男性和3名女性患者,年龄从14岁到59岁(平均,34.4年)。没有患者具有镰状细胞特征。诊断基于8例患者的根治性或部分肾切除术标本和1例的活检标本。肿瘤大小从2.5到7.2cm(平均,2.8厘米)。随访6~36个月,9例患者5例,24个月无肿瘤复发或转移,1例发生肺转移。患者随后接受转移性肿瘤切除治疗,随后接受克唑替尼靶向治疗。12个月后他还活着没有肿瘤.组织学上,肿瘤表现出多种模式的混合生长,包括乳头状的,固体,管状,管系,cribriform,和绳索,通常设置在粘液背景中。肿瘤细胞主要具有嗜酸性的细胞质。集中,清晰的细胞质,具有极化的细胞核和核下液泡(n=1),在肿瘤细胞上观察到苍白的泡沫状细胞质(n=1)。活检的肿瘤显示细长的小管与平淡的梭形细胞融合在一起。其他常见和不常见的特征包括:晶状体微钙化(n=5),横纹肌样细胞(n=4),突出的胞浆内液泡(n=4),突出的慢性炎症浸润(n=3),印戒细胞形态(n=2),和多形性细胞(n=2)。通过免疫组织化学,所有9例肿瘤ALK(5A4)均为弥漫性阳性,4/8例受检病例对TFE3蛋白有反应性.通过荧光原位杂交分析,在所有9个肿瘤中都鉴定了ALK重排;测试的肿瘤中没有一个携带TFE3重排(0/4)或染色体7和17的获得(0/3)。在所有8例分析的病例中,通过RNA测序鉴定了ALK融合伴侣,包括EML4(n=2),STRN(n=1),TPM3(n=1),KIF5B(n=1),HOOK1(n=1),SLIT1(n=1),和TPM1(3'UTR)(n=1)。我们的研究进一步扩展了ALK-RCC的形态和分子遗传谱。
ALK-rearranged renal cell carcinoma (ALK-RCC) is rare, molecularly defined RCC subtype in the recently published fifth edition of World Health Organization classification of tumors. In this study, we described 9 ALK-RCCs from a clinicopathologic, immunohistochemical, and molecular genetic aspect, supporting and extending upon the observations by previous studies regarding this rare subgroup of RCC. There were 6 male and 3 female patients with ages ranging from 14 to 59 years (mean, 34.4 years). None of the patients had sickle cell trait. The diagnosis was based on radical or partial nephrectomy specimen for 8 patients and on biopsy specimen for 1. Tumor size ranged from 2.5 to 7.2 cm (mean, 2.8 cm). Follow-up was available for 6 of 9 patients (6-36 months); 5 had no tumor recurrence or metastasis and 1 developed lung metastasis at 24 months. The patient was subsequently treated with resection of the metastatic tumor followed by crizotinib-targeted therapy, and he was alive without tumor 12 months later. Histologically, the tumors showed a mixed growth of multiple patterns, including papillary, solid, tubular, tubulocystic, cribriform, and corded, often set in a mucinous background. The neoplastic cells had predominantly eosinophilic cytoplasm. Focally, clear cytoplasm with polarized nuclei and subnuclear vacuoles (n = 1), and pale foamy cytoplasm (n = 1) were observed on the tumor cells. The biopsied tumor showed solid growth of elongated tubules merging with bland spindle cells. Other common and uncommon features included psammomatous microcalcifications (n = 5), rhabdoid cells (n = 4), prominent intracytoplasmic vacuoles (n = 4), prominent chronic inflammatory infiltrate (n = 3), signet ring cell morphology (n = 2), and pleomorphic cells (n = 2). By immunohistochemistry, all 9 tumors were diffusely positive for ALK(5A4) and 4 of 8 tested cases showed reactivity for TFE3 protein. By fluorescence in situ hybridization analysis, ALK rearrangement was identified in all the 9 tumors; none of the tested tumors harbored TFE3 rearrangement (0/4) or gains of chromosomes 7 and 17 (0/3). ALK fusion partners were identified by RNA-sequencing in all 8 cases analyzed, including EML4 (n = 2), STRN (n = 1), TPM3 (n = 1), KIF5B (n = 1), HOOK1 (n = 1), SLIT1 (n = 1), and TPM1(3\'UTR) (n = 1). Our study further expands the morphologic and molecular genetic spectrum of ALK-RCC.